13-3: Eukaryotic Regulation
EUKARYOTIC REGULATION
Genome Organization at the DNA Level
In prokaryotes, coding sequences are uninterrupted
In eukaryotes, most DNA does NOT encode protein or RNA, and those that do may be interrupted by
long stretches of noncoding DNA = introns
1) Tandemly Repetitive DNA

10-25% of total DNA in higher eukaryotes is Satellite DNA = highly repetitive DNA
consisting of short unusual nucleotide sequences that are tandemly repeated 1000’s of times

Is not transcribed and its function is not known

Commonly found at the tips and centromeres
o
Telomeres = series of short tandem repeats at the ends of eukaryotic chromosomes
that prevents chromosomes from shortening with each replication cycle
2) Interspersed Repetitive DNA

Repeated units, 100’s or 1000’s of base pairs long, dispersed at random intervals throughout
the genome

25-40% in mammals
3) Transposons = specific DNA sequences that have the ability to move within and between
chromosomes (a.k.a. “movable elements” or “jumping genes”)

Insertion at a new locus may alter the function of neighboring genes, usually decreasing
their expression

May play a driving role in evolution
4) Unique Noncoding DNA

Genes = 1.5% of the genome and repetitive DNA = 44% of human DNA

Remainder is still a mystery
Cellular Differentiation = divergence in structure and function of different cell types, as they become
specialized during an organism’s development

Needed because most cells in a multicellular organism contain the entire genome, but do not want
to express the entire thing

Requires that gene expression be controlled

The control can be at any step in the protein synthesis pathway

Usually it is DNA transcription that is controlled
Pre-Transcriptional CONTROLS
Usually done through chromatin modification
1) Heterochromatin = stays tightly coiled, blocking RNA polymerase and transcription
Ex. Barr Bodies = entire inactivated X chromosomes in female mammals
2) EPIGENETIC INHERITANCE = patterns of inheritance that do not depend on the genes
themselves
a. DNA Methylation

The addition of methyl groups (-CH3) to the tails of histones

Blocks the attachment of RNA Polymerase

Good for long-term control  ensures that once a gene is off, it stays off

Occurs early in embryonic development  part of cell specialization

Patterns are inherited
Genomic Imprinting = process that induces intrinsic changes in chromosomes inherited from males and
females

Causes certain genes to be differently expressed in the offspring depending upon whether the
alleles were inherited from the mom or the dad’s cell

Ex. Deletion on Chromosome 21
o
If inherited from father source: Prader-Willi Syndrome

Symptoms: mental retardation, hunger, short stature, and unusually small hands
and feet
o
If inherited from maternal source: Angelman Syndrome

Symptoms: uncontrollable spontaneous laughter, jerky movements, and other
motor and mental symptoms

Ex. Fragile X Syndrome
o
Affects 1 in every 1500 males and one in every 2500 females
o
Most common cause of mental retardation
o
The “fragile X” is an abnormal X chromosome, the tip of which hangs on the rest of the
chromosome by a thin DNA thread

May be result of imprinting, since it is more likely to appear if the abnormal X is
inherited from the mother rather than the father
b. Histone Acetylation

Acetyl groups (-COCH3) are added to the tails of histones

This prevents the histones from tightly binding to the DNA strands, allowing RNA
polymerase easier access to the gene

Keeps genes “ON”
TRANSCRIPTIONAL CONTROLS

Controlled by DNA-binding proteins, especially transcription factors

Recall a eukaryotic gene has a Promoter at the 5’ end with a TATA box where transcription
factors bind, which in turn draw in RNA polymerase and help it attach; the structural gene (which
also contains noncoding introns) and a terminator.

Transcription Activator = a DNA-binding protein that is necessary for transcription to occur

Enhancers = regions of DNA where transcription activator binds, upstream from the promoter

Cause a hairpin loop in the DNA that brings the transcription activators into contact with the rest
of the transcription factor complex  turns gene “on”

Binding of repressors to silencers within the promoter inhibit transcription  turn gene “off”

Coordinately Controlled Genes
o
Eukaryotic genes coding for enzymes of a metabolic pathway are often scattered over
different chromosomes (unlike prokaryotes).
o
To make all the enzymes for a pathway in synchrony, each gene is associated with the
same type of control elements (enhancers and repressors) which are turned on by the
same activator and turned off by the same inhibitor.
POST-TRANSCRIPTIONAL CONTROLS

Occurs in the nucleus

Includes alternative mRNA splicing and controlling the speed with which mRNA leaves the
nucleus
Regulation of mRNA Degradation

While prokaryotic mRNA is broken down after only a few minutes, eukaryotic mRNA can last
for several hours or even weeks
Small RNA (sRNA) Molecules Regulate Gene Expression

Only 1.5% of transcribed DNA codes for protein and the remainder is used to form sRNA
molecules

These may regulate gene expression by:
1. Altering the compacting of DNA so that some genes are inaccessible to the transcription
machinery of the cell
2. Becoming microRNAs (miRNAs) = small snippets of RNA that can bind to and prevent
translation of an mRNA strand in the cytoplasm
3. Becoming small-interfering RNAs (siRNAs) that join with an enzyme (called RNAinduced silencing complex or RISC) to form an active silencing complex. This finds
specific mRNAs in the cell and breaks them down, preventing their expression.

These processes are referred to as RNA interference  act like a dimmer switch on gene
expression

Hope is that they may be used to suppress disease-causing genes in the future.
TRANSLATIONAL CONTROL

Presence of the 5’ cap and poly-A tail lengthen the amount of time a transcript is allowed to
continue to be translated
o
Without them, the mRNA strand is broken down
POST-TRANSLATIONAL CONTROL

Regulated by proteases = enzymes that break down proteins

Contained in proteasomes

Proteins are tagged with a signaling protein that causes it to be taken up and destroyed in a
proteasome